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Biomedical subjects

C Go

Publications and source records attributed to C Go.

15 recordsLinked to original sources

A unique strategy of host colony exploitation in a parasitic ant: workers of Polyrhachis lama rear their brood in neighbouring host nests.

The formicine ant Polyrhachis lama is a social parasite, exploiting its ponerine host ant species Diacamma sp. In most social parasitic associations, the parasitic species are closely related to their host species group, evolving directly from independent ancestors of the host species. However, in the Polyrhachis lama- Diacamma sp. association, the associated species belong to different ant subfamilies. Based on preliminary field surveys, we had presumed that P. lama might have given up its reproductive division of labour, i.e. workers would be able to produce males as well as workers and females parthenogenetically. In this study, this hypothesis was disproved: Polyrhachis lama workers cannot be fertilized and are only able to produce males. In the host-parasite association originating from nests possessing a P. lama queen, workers penetrate surrounding Diacamma sp. nests, carrying brood for rearing within these satellite nests. In this peculiar way, a single P. lama colony is able to exploit several Diacamma sp. colonies simultaneously.

Animals↗

Measurement of TG synthesis and turnover in vivo by 2H2O incorporation into the glycerol moiety and application of MIDA.

A method is presented for measurement of triglyceride (TG) synthesis that can be applied to slow-turnover lipids. The glycerol moiety of TG is labeled from 2H2O, and mass isotopomer distribution analysis (MIDA) is applied. Mice and rats were given 4-8% 2H2O in drinking water; TG-glycerol was isolated from adipose and liver during < or =12-wk of 2H2O labeling. Mass isotopomer abundances in the glycerol moiety of TG were measured by GC-MS. The combinatorial pattern of isotopomers revealed the number of H atoms in glycerol incorporating label from 2H2O (n) to be 3.8-4.0 of a possible 5 for adipose tissue and 4.6-4.8 for liver TG. Hepatic TG-glycerol in fact reached 97% predicted maximal value of label incorporation (4.4-4.6 x body 2H2O enrichment), indicating near-complete replacement of the liver TG pool. Label incorporation into adipose tissue revealed turnover of mesenteric TG to be faster (k = 0.21 day-1) than other depots (k = 0.04-0.06 day-1) in mice. TG isolated from subcutaneous depots of growing adult rats plateaued at 85-90% of calculated maximal values at 12 wk (k = 0.05 day-1), excluding significant dilution by unlabeled alpha-glycerol phosphate. Turnover of plasma TG, modeled from 2H incorporation over 60 min, was 0.06 min-1 (half-life 11.5 min). In summary, use of 2H2O labeling with MIDA of TG-glycerol allows measurement of new alpha-glycerol phosphate-derived TG synthesis and turnover. The hypothesis that mesenteric TG is more lipolytically active than other depots, previously difficult to prove by isotope dilution techniques, was confirmed by this label incorporation approach.

Adipose Tissue↗

Aberrant cell cycle progression contributes to the early-stage accelerated carcinogenesis in transgenic epidermis expressing the dominant negative TGFbetaRII.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) have been found in various malignant tumors, suggesting that loss of TGFbeta signaling plays a causal role in late-stage cancer development. To test whether loss of TGFbetaRII is involved in early-stage carcinogenesis, we have generated transgenic mice expressing a dominant negative TGFbetaRII (deltabetaRII) in the epidermis. These mice exhibited an increased susceptibility to chemical carcinogenesis protocols at both early and late stages. In the current study, parameters for cell cycle progression and chromosome instability were analysed in deltabetaRII tumors. DeltabetaRII papillomas showed an increased S phase in flow cytometry. Bromodeoxyuridine (BrdU) labeling and mitotic indices in deltabetaRII papillomas also showed a threefold increase compared to papillomas developing in non-transgenic mice. When papillomas further progressed to squamous cell carcinomas (SCC), both control and deltabetaRII SCC showed similar BrdU labeling indices and percentages of S phase cells. However, deltabetaRII SCC cells showed a sixfold increase in the G2/M population. Mitotic indices in deltabetaRII SCC also showed a threefold increase compared to non-transgenic SCC. Consistent with a perturbed cell cycle, deltabetaRII papillomas and SCC showed reduced expression of the TGFbeta target genes p15 (INK4b), p21 (WAF-1) and p27 (Kip1), inhibitors of cyclin-dependent kinases (cdks). However, most deltabetaRII papilloma cells exhibited normal centrosome numbers, and deltabetaRII SCC exhibited a similar extent of centrosome abnormalities compared to control SCC (35-40% cells). Most of deltabetaRII SCC exhibited diploid chromosome profiles. These data indicate that inactivation of TGFbetaRII accelerates skin tumorigenesis at early stages by the acceleration of loss of cell cycle control, but not by increased chromosome instability.

9,10-Dimethyl-1,2-benzanthracene↗

Intracranial complications of acute mastoiditis.

OBJECTIVE: Oral antibiotic use may have changed the incidence and microbiology of otitic intracranial complications. We reviewed cases of acute mastoiditis to document: (1) incidence of intracranial complications; (2) risk factors; and (3) identify pathologic organisms. METHODS: A retrospective study of children at a tertiary care children's hospital with acute mastoiditis from July, 1986 through June, 1998. RESULTS: 118 children with acute mastoiditis were identified. Eight patients (6.8%), ages 20 months to 14 years, had intracranial complications related to acute mastoiditis. Three children had a sigmoid sinus thrombosis, two children had an epidural abscess, and two children had both complications of sigmoid sinus thrombosis and epidural abscess, and a sigmoid sinus thrombosis and meningitis was present in one child. Pre-admission oral antibiotics were administered for an average of 10 days in seven of the eight patients. Persistent otorrhea and/or otalgia were present in all patients. Intraoperative cultures were negative in four cases (50%). Organisms isolated included: Streptococcus pneumoniae (2); Proteus mirabilis (1); Pseudomonas aeruginosa (1); and coagulase negative Staphylococcus (1). Multi-drug resistant organisms were documented in only one case. All patients underwent a contrast enhanced CT of the temporal bones and brain. Surgical management included complete mastoidectomy in all patients and a pressure equalization tube in seven of the eight cases. CONCLUSIONS: Our review did not document an increase in the incidence of otitic intracranial complications. Persistent otalgia or otorrhea while on oral antibiotics with associated neurologic symptoms are ominous signs suggestive of a complication. Multi-drug resistant organisms are uncommon whereas negative intraoperative cultures are common.

Acute Disease↗

Management and complications of congenital dacryocele with concurrent intranasal mucocele.

INTRODUCTION: The association of dacryocele and intranasal mucocele has been previously reported. Its incidence and optimal treatment are unknown. PATIENTS AND METHODS: A retrospective review of 22 patients with 30 dacryoceles was performed to determine the mean age at presentation, sex distribution, and prevalence of associated intranasal mucocele, associated dacryocystitis, and respiratory distress. The components of the examination, ancillary tests, treatment modalities, and treatment outcomes were then summarized. RESULTS: Unilateral dacryoceles were seen in 16 (73%) of the infants, and bilateral dacryoceles were seen in 6 (27%) of the infants. Four (25%) of the 16 patients who initially had unilateral dacryoceles later developed bilateral dacryoceles. Dacryocystitis, preseptal cellulitis, or both were present on presentation or developed in 18 (60%) of 30 dacryoceles. Nasal endoscopy was performed on 13 (59%) of 22 patients. Nasal examination with nasal speculum and headlight was performed on 7 patients (32%). A concurrent intranasal mucocele was diagnosed in 23 (77%) of 30 dacryoceles. Respiratory distress arose in 5 (71%) of 7 patients with bilateral intranasal mucoceles and in 2 (22%) of 9 patients with a unilateral intranasal mucocele. Thirty-four procedures were performed. Seven dacryoceles (21%) were treated with nasolacrimal duct probing under topical anesthesia. Another one (3%) was treated with needle aspiration with later definitive therapy. All other procedures were managed under general anesthesia. These included 2 nasolacrimal duct probings (6%), 2 probings with silicone tube placement (6%), 10 probings with intranasal mucocele marsupialization and silicone tube placement (29%), and 12 probings with marsupialization alone (35%). Two (29%) of the 7 probings performed under topical anesthesia failed, whereas all other procedures were successful. One dacryocele spontaneously resolved. CONCLUSIONS: Congenital dacryoceles are commonly associated with intranasal mucoceles, dacryocystitis, and preseptal cellulitis. Respiratory distress is common in bilateral cases. Bilateral nasolacrimal duct probing should be considered in unilateral cases because of the high incidence of occult contralateral involvement.

Endoscopy↗

Blocking transforming growth factor beta signaling in transgenic epidermis accelerates chemical carcinogenesis: a mechanism associated with increased angiogenesis.

Mutations in the transforming growth factor beta type II receptor (TGF-betaRII) have been identified in human cancers, which suggests a causal role for the loss of TGF-betaRII in cancer development. To directly test this in vivo, we have generated transgenic mice expressing a dominant negative TGF-betaRII (delta betaRII) in the epidermis, using a truncated mouse loricrin promoter (ML). ML.delta betaRII transgenic mice exhibited a thickened skin due to epidermal hyperproliferation. When these mice were subjected to a standard two-stage chemical carcinogenesis protocol, they exhibited an increased sensitivity, with an earlier appearance and a 2-fold greater number of papillomas than control mice. In addition, papillomas in control mice regressed after termination of 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment; whereas ML.delta betaRII papillomas progressed to carcinomas. Furthermore, TPA promotion alone induced papilloma formation in ML.delta betaRII mice, which suggests an initiating role for delta betaRII in skin carcinogenesis. ML.delta betaRII tumors also exhibited increased neovascularization and progressed to metastases, although the primary tumors were still classified as carcinoma in situ or well-differentiated carcinomas. Increased expression of vascular endothelial growth factor, an angiogenesis factor, and decreased expression of thrombospondin-1, an angiogenesis inhibitor, were also observed in ML.delta betaRII tumors. The increased angiogenesis correlated with elevated endogenous TGF-beta1 in ML.delta betaRII tumors. These data provide in vivo evidence that inactivation of TGF-betaRII accelerates skin carcinogenesis at both earlier and later stages, and increased angiogenesis is one of the important mechanisms of accelerated tumor growth and metastasis.

Animals↗

Cytoskeleton-dependent activation of the inducible nitric oxide synthase in cultured aortic smooth muscle cells.

1. Vascular endothelial and smooth muscle cells generate nitric oxide (NO) via different nitric oxide synthase (NOS) isozymes. Activation of the endothelial constitutive NOS (ecNOS) contributes to the maintenance of cardiovascular homeostasis, whereas expression of the endotoxin- and cytokine-inducible pathway (iNOS) within the vascular smooth muscle is thought to be responsible for the cardiovascular collapse which occurs during septic shock and antitumour therapy with cytokines. Since the cytoskeleton is involved in the activation of certain genes and in some effects of endotoxin in macrophages, we investigated the role of microtubules and microfilaments in the activation of the NO pathway in cultured vascular cells. 2. Depolymerization of microtubules by either nocodazole or colchicine prevented lipopolysaccharide (LPS)- and interleukin-1 beta-induction of NO-dependent cyclic GMP accumulation. Steady state levels of iNOS mRNA, assessed by Northern blot and RT-PCR, and iNOS protein, assessed by Western blotting, were also decreased by either colchicine or nocodazole treatment. 3. Taxol enhanced microtubule polymerization alone, and prevented microtubule depolymerization elicited by nocodazole and colchicine. Associated with its effect on microtubule assembly, taxol prevented the inhibitory effects of nocodazole and colchicine on cyclic GMP accumulation and iNOS mRNA levels. 4. Disruption of microfilaments by cytochalasins had no inhibitory effect on the activation of the inducible NO pathway. 5. In contrast to cytokine-stimulated smooth muscle cells, modulation of either microtubule or microfilament assembly did not affect the constitutive NO pathway in endothelial cells, as endothelial cell- and NO-dependent cyclic GMP accumulation in endothelial-smooth muscle co-cultures remained unchanged. 6. Our findings demonstrate that microtubules play a prominent role in the activation of the inducible NO pathway in response to inflammatory mediators in smooth muscle cells but not of the constitutive synthesis of NO in endothelial cells.

Animals↗

Anergized T cell clones retain their cytolytic ability.

CD4+ T cells have been described to have both helper and lytic function. The helper function of Th1 cells in particular can be inactivated by inducing the T cell into a state of nonresponsiveness in which the T cell is no longer capable of producing IL-2 or proliferating in an autocrine way to a conventional antigenic stimulus. To determine whether the lytic ability of Th1 cells can also be rendered nonfunctional upon anergy induction, we induced Th1 clones into a nonresponsive state and tested their ability to lyse target cells in an Ag-specific and MHC class II-restricted manner. We show that cells newly induced into an anergic state were able to lyse target cells nonspecifically. This effect was short-lived and after resting in culture media, the cells regained their ability to lyse target cells in an Ag/MHC-specific manner, and this ability was comparable to normal resting T cells. In contrast, the helper function of these cells remained nonresponsive, and the cells were unable to proliferate or to secrete IL-2 in response to the same antigenic stimulus used for lysis. Therefore, the lytic pathway appears to be regulated separately from the proliferative/lymphokine pathway(s) and is not affected long-term by an anergic stimulus.

Animals↗

Differential induction of transcription factors that regulate the interleukin 2 gene during anergy induction and restimulation.

T cell activation requires two distinct signals. The first is delivered through the antigen-specific T cell receptor (TCR), and the second is provided by costimulatory molecule(s) present on the surface of the antigen-presenting cell (APC). Stimulation of T helper type 1 T cell clones through the TCR in the absence of the costimulatory activity results in a lack of interleukin 2 (IL-2) secretion and proliferation, and the induction of a long-lived state of nonresponsiveness, termed anergy. In this study, we have examined the transcription factors involved in IL-2 gene expression that are expressed after stimulation of normal T cell clones through the TCR with and without engagement of the necessary costimulatory molecule(s). Antigen-specific activation of the clones results in the induction of a similar pattern of transcription factors that have been previously shown to regulate IL-2 expression. In contrast, antigen presentation by chemically fixed APC, a condition that results in T cell anergy, induces neither NF-AT nor one of the two NF-kappa B binding factors. Thus, the failure to express IL-2 during the induction of T cell anergy may be attributed to the absence of these two transcription factors. When anergized T cells are restimulated with antigen and conventional APC, they induce the transcription factors associated with IL-2 expression, but they fail to synthesize measurable IL-2. Taken together, these data indicate that the control of IL-2 gene expression during anergy induction and during normal stimulation of anergized cells are distinct, and suggest the presence of additional regulatory elements in the IL-2 gene.

Animals↗

The development of humoral immunity to tissue-specific tubular basement membrane alloantigens after renal transplantation across the major histocompatibility barrier in rats immunomodulated with blood transfusions and cyclosporin.

The development of a humoral immune response to the tubular basement membrane (TBM) alloantigen of Brown-Norway (BN) rat kidneys was studied after transplantation of BN rat kidneys into bilaterally nephrectomized Lewis (LEW) rats. The LEW rat recipients consisted of four groups receiving no form of immunosuppression, pretransplantation cyclosporin alone, or pretransplantation donor-specific or donor-nonspecific transfusions combined with cyclosporin. The latter two regimens induce indefinite allograft survival in the majority of recipients. Circulating antibody to collagenase-solubilized BN rat renal basement membrane (CS-BN-RBM) was present in all four groups of transplant recipients within 1 week after transplantation, and no significant differences in antibody levels were noted between rats receiving no immunosuppression (survival of 1-2 weeks) and the groups of rats who received various immunosuppressive regimens and survived longer. Circulating antibody to BN-CS-RBM continued to increase in quantity in the cyclosporin-treated group until the time of death (2-10 weeks post-transplantation). In the much longer lived combined transfusion and cyclosporin-treated groups, circulating antibody to BN-CS-RBM generally attained a maximum at approximately 2 to 4 months post-transplantation and then plateaued or decreased somewhat before the time of death (3-16 months post-transplantation). No correlation was found between quantity of circulating anti-BN-CS-RBM antibody and post-transplantation survival. Comparative study of the quantity of circulating antibody to BN-CS-RBM (the presumed nephritogenic antigen of experimental tubulointerstitial nephritis in the BN rat) in serum from transplant recipients as compared to serum from BN rats with severe experimental tubulointerstitial nephritis (TIN) (as induced by immunization with heterologous TBM antigens) demonstrated a greater quantity of potentially nephritogenic antibody circulating in transplant recipients than in BN rats with experimental TIN. Histologically, the transplanted kidneys in immunomodulated recipients demonstrated focal chronic interstitial inflammatory infiltrates with tubular atrophy and relative sparing of the glomeruli. The development of immune responses to tissue-specific alloantigens may become of clinical significance as graft-survival times are increased.

Animals↗

Intratracheal aerosolization of endotoxin (LPS) in the rat: a comprehensive animal model to study adult (acute) respiratory distress syndrome.

The aim of the study was to extend existing evidence that intratracheal aerosolization of LPS may serve as a very relevant model to study ARDS. The authors investigated the sequence of pathogenic events reflected by changes in levels of tumor necrosis factor alpha (TNF alpha), surfactant-associated protein A (SP-A) in BAL fluid, in addition to cell count, edema formation, and respiratory function. Within 24 h following intratracheal aerosolization of LPS in the rat, ARDS could be diagnosed according to the lung injury score for patients. This score includes the extent of the inflammatory density on chest X-rays, the severity of hypoxemia, the decline in lung compliance, and the level of PEEP (positive end expiratory pressure). In addition, other typical features of human ARDS appeared to be present in this model: (1) increased microvascular permeability reflected by edema, elevated levels of protein and of LDH, and increased numbers of PMNs in BAL fluid; (2) high levels of TNF alpha in BAL fluid preceding the appearance of PMNs; (3) changes in breathing pattern and a gradual development of respiratory failure with decreased compliance. SP-A levels in BAL fluid doubled within one hour after LPS administration, suggesting that this collectin may play a role in the immediate inflammatory response. Taken together, the findings presented here suggest that intratracheal LPS administration mimics the clinical development of ARDS very closely.

Administration, Inhalation↗